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Biomed Pharmacother. 2018 May;101:510-527. doi: 10.1016/j.biopha.2018.02.105. Epub 2018 Mar 22.

Involvement of growth factors in diabetes mellitus and its complications: A general review.

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Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China.
Joint Laboratory of Traditional Natural Medicine, Yunnan Minzu University, Kunming, 650500, China.
Department of Pharmacology, Zunyi Medical University, Guizhou 563003, China.
Department of Pharmacology, Xian Jiaotong University, Xian 710049, China.
Cell and Immune Center, Shanghai Jiaotong University, Shanghai 200240, China.
Department of Obstetrics and Gynecology, Shanghai Fifth People's Hospital 200240, China.
State Key Laboratory of Natural Medicines and Institute of Pharmaceutical Science, China Pharmaceutical University, Nanjing, China. Electronic address:
Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China. Electronic address:


Diabetes mellitus (DM) is a major endocrine metabolic disease and is marked by a lack of insulin. The complication of DM is one of the most difficult problems in medicine. The initial translational studies revealed that growth factors have a major role in integrating tissue physiology and in embryology as well as in growth, maturation and tissue repair. In some tissues affected by diabetes, growth factors are induced by a relative deficit or excess. Fibroblast growth factor 21 (FGF21) is a promising regulator of glucose and lipid metabolism with multiple beneficial effects including hypoglycemic and lipid-lowering. Vascular endothelial growth factor (VEGF) is a potent angiogenic and vascular permeability factor and is implicated in both of these complications in diabetes. Increase or decrease in the production of transforming growth factor-β1 (TGF-β1) has been associated with diabetic nephropathy and retinopathy. The insulin-like growth factor-I (IGF-I) is a naturally-occurring single chain polypeptide which has been widely used in the treatment of diabetic glomerular and renal tubular injuries. This review summarizes the recent evidences for an involvement of growth factors in diabetic complications, focusing on their emergence in sequence of events leading to vascular complications or their potential therapeutic role in these diseases. Growth factor therapy in diabetic foot ulcers is already a clinical reality. As methods to finely regulate growth factors in a tissue and time-specific manner are further developed and tested, regulation of the growth factor to normal level in vivo may well become a therapy to prevent and treat diabetic complications.


Diabetic complications; Fibroblast growth factor 21; Growth factors; Transforming growth factor-β; Vascular endothelial growth factor

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